Project Summary/Abstract Dr. Cathy Carlson is an experienced, ACVP-boarded veterinary pathologist and orthopaedic researcher who is a tenured full professor in the College of Veterinary Medicine at the University of Minnesota. Although Dr. Carlson is an active research collaborator, gradually increasing service commitments and other responsibilities have prevented her from having a more central role in research in recent years. In this application, she requests 50% salary support for two years while she acquires new knowledge in the area of high field magnetic resonance imaging (MRI) and applies this knowledge to the development of methods to diagnose subclinical lesions of osteochondrosis. For these studies, she will use a well-characterized animal model of osteochondrosis (spontaneous disease in young pigs) with which she has considerable expertise. She will be assisted in these studies by her primary mentor, Dr. Michael Garwood, who is an expert in the area of high field MRI technique development, and her mentoring committee: Dr. Jutta Ellermann (expert in human orthopaedic MRI, including osteochondrosis), Dr. Denis Clohisy (chair of the Department of Orthopaedic Surgery and experienced orthopaedic researcher), and Dr. Jack Lewis (cartilage matrix biology and biomechanics expert). In the proposed, highly innovative studies, the extensive knowledge and experience that Dr. Carlson has with a well-documented animal model of osteochondrosis will be combined with the state-of- the-art high field MRI expertise of the mentor group to identify subclinical lesions of osteochondrosis in intact joints of young pigs, in which the disease occurs with nearly 100% prevalence. Newly developed high field MRI techniques will be used to detect and characterize early damage to the cartilage. The specific aims of the proposed studies are to 1) Develop high-field MRI techniques to identify and characterize subclinical lesions of osteochondrosis, (locally extensive areas of cartilage necrosis), in intact and disarticulated specimens of distal humerus and distal femur (most common predilection sites in both swine and humans) from young pigs; 2) Develop quantitative techniques to characterize the collagen and proteoglycan components of the lesions for comparison with the MRI results; and 3) Develop high-field MRI techniques to identify and map cartilage canal blood vessels and validate these in cleared specimens in which the vessels have been perfused with barium sulfate. This career development award will allow Dr. Carlson the dedicated time to 1) gain expertise in MRI methodology; 2) interact closely with the scientists at the Center for Magnetic Imaging Research; 3) identify and acquire the appropriate porcine specimens for study; 4) assist in interpreting the MRI findings and modifying the techniques through parallel histological studies in the same sites as those evaluated by MRI; and 5) interact with a highly qualified mentor group, the members of which will provide both specific and global input to her proposed research. Dr. Carlson's long-term career goal is to remain in academic research, obtain and maintain RO1 funding for this project, and to devote at least 75% of her effort to research activities. PUBLIC HEALTH RELEVANCE: Project Narrative Osteochondrosis is a focal or multifocal failure in the process of endochondral ossification (conversion of growth cartilage to bone during growth and development) that predisposes the affected site to the formation of a cartilaginous/osteocartilaginous flap (osteochondritis dissecans/OCD), resulting in joint pain and dysfunction. It occurs increasingly commonly in children and young adult patients, and treatment usually includes surgical removal of the flap; however, because of the poor healing qualities of articular cartilage, the affected joint is at risk for the later development of osteoarthritis. If,as proposed in the present application, methods could be developed to diagnose the subclinical disease (prior to the formation of the flap), it is very likely that temporary lifestyle changes, designed to decrease joint trauma, would allow complete and spontaneous healing of the affected site.